- Email: [email protected]
Carcinoembryonic antigen of cerebrospinal fluid predict prognosis of leptomeningeal metastasis from non-small cell lung cancer
abstracts Funding: This study was partially supported by Shanghai Committee of Science and technology (No. 14411970800). The funder had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Disclosure: All authors have declared no conflicts of interest.
1563P
Carcinoembryonic antigen of cerebrospinal fluid predict prognosis of leptomeningeal metastasis from non-small cell lung cancer
Background: Leptomeningeal metastasis (LM) is a detrimental complication of patients with non-small cell lung cancer (NSCLC) and its incidence has increased due to recent improvements in survival. The aim of this study was to identify the clinicolpathological features and prognostic factors related to overall survival in NSCLC patients with LM. Methods: Seventy-four consecutive patients diagnosed with LM from NSCLC between 2009 and 2018 in Guangdong Sanjiu Brain Hospital were retrospectively reviewed. Results: Median KPS at diagnosis of LM were 60 (range, 20-90). Forty-seven (63.5%) patients harboring epidermal growth factor receptor (EGFR) or anaplasticlymphoma kinase (ALK) mutation while other twenty-seven patients (36.5%) were wild type or unknown status. Local treatment for LM consisted of whole-brain radiotherapy (WBRT) (52.7%), ventriculoperitoneal (VP) shunt (6.8%) and external drainage (6.8%). Systematic therapy for LM included EGFR or ALK tyrosine kinase inhibitors (TKI) (59.5%), chemotherapy (40.5%) and bevacizumab (8.1%). The median overall survival from diagnosis of LM to death was 8.1 months (95% confidence interval: 5.2 to 11.0). Patients with high Cerebrospinal Fluid (CSF) carcinoembryonic antigen (CEA) level (>50ng/ml) had worse prognosis compared with those low CSF CEA level (50ng/ml) ones (p ¼ 0.02). However, there was no significant difference in survival between patients with high serum CEA and those with low serum CEA (p ¼ 0.645). EGFR/ALK mutation and EGFR/ALK TKI after LM were also identified as variables that had prognostic influence on survival, while KPS, concurrent brain metastasis, WBRT and chemotherapy had no prognostic value for survival. Conclusions: Median overall survival was higher than historical experience in this retrospective analysis. It is CSF CEA level, but not serum CEA level that correlated with prognosis for LM from NSCLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1564P
Liquid biopsy in clinical pratice of non-small cell lung cancer (NSCLC): A multi-institutional experience
G. De Maglio1, G. Pasello2, A. Follador3, G. Nardo4, F. Cortiula5, A. Del Conte6, A. D’Urso7, G. Petros8, S. Girlando9, M. Miorin10, V. Polo11, E. Scquizzato12, G. Settanni13, V. Picece14, A. Veccia15, S. Indraccolo16 1 Department of Pathology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, 2Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy, 3Oncology Department, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy, 4U.O.C. Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, 6S.O.C. Oncologia Medica e dei Tumori Immunocorrelati, Centro di Riferimento Oncologico (CRO) – IRCCS, Aviano, Italy, 7U.O.C. Anatomia Patologica, ULSS1 Dolomiti - Presidio Ospedaliero di Feltre, Feltre, Italy, 8U.O.C. Oncologia, ULSS1 Dolomiti - Presidio Ospedaliero di Feltre, Feltre, Italy, 9Ospedale Santa Chiara, Trento, U.O. Anatomia Patologica, Trento, Italy, 10SSD Genetica medica, AAS5 - Presidio Ospedaliero di Pordenone, Pordenone, Italy, 11Oncology Unit, AULSS 2 Marca Trevigiana, Ca’ Foncello Hospital, Treviso, Italy, 12Dipartimento Interaziendale di Anatomia Patologica, ULSS 2 Marca Trevigiana, Treviso, Italy, 13Servizio di Anatomia-Istologia Patologica, IRCCS Ospedale Sacro Cuore Don Calabria - Negrar, Italy, 14Dipartimento di Oncologia Medica, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy, 15U.O. Oncologia Medica, Ospedale Santa Chiara, Trento, Italy, 16U.O.C. Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy Background: Circulating tumor DNA (ctDNA) from liquid biopsy is a source of tumor genetic material for EGFR testing in NSCLC when resistance to I-II generations TKItherapies occurs or upfront, in absence of tissue biopsy. A multi-regional survey for patients treated with EGFR TKI from January to December 2018 was conducted regarding use of liquid biopsy for NSCLC in clinical practice. Methods: Aim of the study was to describe EGFR testing workflow by liquid biopsy in clinical setting. Seven major lung-cancer centers in North Eastern Italy participated to the survey. Results: Overall 316 patients (360 samples) have been screened for ctDNA EGFR, with a medium number of 1.1 samples/patient. All institutions reported EGFR as the main gene tested for clinical purposes in plasma samples of NSCLC, other genes (i.e. KRAS/ BRAF) were occasionally tested upon oncologist request. Seven out of seven (100%) centers used commercially available real time CE-IVD tests. NGS or droplet digital
v644 | NSCLC, Metastatic
PCR were used by one center each, as confirmation methods. In all institutions blood drawing was performed in the same hospital of EGFR testing (in 6/7 - 86%- centers in the Medical Oncology Unit), and plasma separated within 2 hours. EGFR testing was performed in the Surgical Pathology Unit and report edited within 24 hours in 3/7 (43%) centers and within 3-5 working days in 4/7 (57%) centers. Among all, 108 (34%) patients were tested at the time of diagnosis with an EGFR mutation rate of 15%. At progression to TKI treatment, 208 (66%) patients were tested. T790M positive rate was 55/122 (45%). Inconclusive cases (negative for both T790M and known actionable mutation) were 86 (41%). All centers declared that histo/cytological re-biopsy was suggested in these cases. Conclusions: Real-world experiences about EGFR testing in liquid biopsies revealed homogeneous habits among interviewed centers, according to national guidelines and literatures data. The consistent number of liquid biopsies at the time of diagnosis mainly refers to some reference centers that collect specimens from several institutions. However it might impose a revision of bronchoscopy workflows in order to obtain better samples suitable both for cito-histological diagnosis and molecular profiling. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1565P
A phase III study comparing SB8, a proposed bevacizumab biosimilar, and reference bevacizumab in patients with metastatic or recurrent non-squamous NSCLC
M. Reck1, A. Luft2, I. Bondarenko3, S. Shevnia4, D. Trukhin5, N.V. Kovalenko6, K. Vacharadze7, F. Andrea8, A. Hontsa9, J. Choi10, D. Shin11 1 Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany, 2Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russian Federation, 3Oncology and Medical Radiology Department, Dnipropetrovsk City Multidisciplinary Clinical Hospital N4, Dnipro, Ukraine, 4Department of Chemotherapy, Podillia Regional Oncology Center, Vinnytsia, Ukraine, 5Oncology Department, Odessa Regional Oncology Center, Odessa, Ukraine, 6Oncology, Volgograd Regional Clinical Oncology Dispensary, Volgograd, Russian Federation, 7Department of Phthisiatry, Research Institute of Clinical Medicine, agos Kor anyi Tbilisi, Georgia, 8Department of Pulmonary Class and Bronchology, Orsz TBC e´s Pulmonol ogiai Inte´zet, Budapest, Hungary, 9Day Staing Department, Chernivtsi 10 Regional Oncology Center, Chernivtsi, Ukraine, Biometrics, Samsung Bioepis Co., Ltd., Suwon, Republic of Korea, 11Medical Affairs, Samsung Bioepis Co., Ltd., Suwon, Republic of Korea Background: SB8 is a proposed biosimilar of the reference bevacizumab (BEV). This study compared the efficacy, safety, pharmacokinetics (PK), and immunogenicity of SB8 to BEV in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC). Methods: In this randomised, double-blind, multicentre study, patients were randomised (1:1) to receive SB8 or BEV with paclitaxel and carboplatin Q3W followed by SB8 or BEV maintenance therapy until disease progression, unacceptable toxicity, death, or 1 year from the randomisation of the last patient. The primary endpoint was the best overall response rate (ORR) by 24 weeks of chemotherapy; risk ratio was analyzed in the full analysis set (FAS) and risk difference was analyzed in the per-protocol set (PPS). Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety, PK, and immunogenicity. Results: A total of 763 patients (SB8, n ¼ 379; BEV, n ¼ 384) were randomized. Baseline characteristics were balanced between SB8 and BEV. In the FAS, the best ORR was 47.6% in SB8 and 42.8% in BEV; the risk ratio was 1.11 and its 90% CI was [0.975, 1.269], which was within the pre-defined equivalence margin of [0.737, 1.357]. In the PPS, the best ORR was 50.1% in SB8 and 44.8% in BEV; the risk difference was 5.3% and its 95% CI was [2.2%, 12.9%], of which the lower margin was contained within and the upper margin was outside the pre-defined equivalence margin of [12.5%, 12.5%]. The secondary efficacy endpoints in the FAS were comparable between SB8 vs BEV: median PFS (8.50 vs 7.90 months), median OS (14.90 vs 15.80 months), and median DOR (5.60 vs 5.85 months). The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between SB8 vs BEV (92.1% vs 91.1%). The most frequently occurring TEAEs were alopecia, anaemia, and nausea. PK parameters (Ctrough and Cmax) and the incidence of overall anti-drug antibodies (16.1% vs 11.0%) were comparable between SB8 vs BEV. Conclusions: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio. Other efficacy endpoints, safety, PK, and immunogenicity were comparable between SB8 and BEV. Clinical trial identification: NCT02754882. Legal entity responsible for the study: Samsung Bioepis Co., Ltd. Funding: Samsung Bioepis Co., Ltd. Disclosure: M. Reck: Honoraria (self), Advisory / Consultancy: Samsung Bioepis Co., Ltd.; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche. J. Choi: Full / Part-time employment: Samsung Bioepis Co., Ltd. D. Shin: Full /
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.085/5578305 by guest on 25 October 2019
J. Zhen, L. Wen, S. Li, M. Lai, C. Zhou, L. Cai Department of Oncology, Guangdong Sanjiu 999 Brain Hospital, Guangzhou, China
Annals of Oncology
1563P
Carcinoembryonic antigen of cerebrospinal fluid predict prognosis of leptomeningeal metastasis from non-small cell lung cancer
Background: Leptomeningeal metastasis (LM) is a detrimental complication of patients with non-small cell lung cancer (NSCLC) and its incidence has increased due to recent improvements in survival. The aim of this study was to identify the clinicolpathological features and prognostic factors related to overall survival in NSCLC patients with LM. Methods: Seventy-four consecutive patients diagnosed with LM from NSCLC between 2009 and 2018 in Guangdong Sanjiu Brain Hospital were retrospectively reviewed. Results: Median KPS at diagnosis of LM were 60 (range, 20-90). Forty-seven (63.5%) patients harboring epidermal growth factor receptor (EGFR) or anaplasticlymphoma kinase (ALK) mutation while other twenty-seven patients (36.5%) were wild type or unknown status. Local treatment for LM consisted of whole-brain radiotherapy (WBRT) (52.7%), ventriculoperitoneal (VP) shunt (6.8%) and external drainage (6.8%). Systematic therapy for LM included EGFR or ALK tyrosine kinase inhibitors (TKI) (59.5%), chemotherapy (40.5%) and bevacizumab (8.1%). The median overall survival from diagnosis of LM to death was 8.1 months (95% confidence interval: 5.2 to 11.0). Patients with high Cerebrospinal Fluid (CSF) carcinoembryonic antigen (CEA) level (>50ng/ml) had worse prognosis compared with those low CSF CEA level (50ng/ml) ones (p ¼ 0.02). However, there was no significant difference in survival between patients with high serum CEA and those with low serum CEA (p ¼ 0.645). EGFR/ALK mutation and EGFR/ALK TKI after LM were also identified as variables that had prognostic influence on survival, while KPS, concurrent brain metastasis, WBRT and chemotherapy had no prognostic value for survival. Conclusions: Median overall survival was higher than historical experience in this retrospective analysis. It is CSF CEA level, but not serum CEA level that correlated with prognosis for LM from NSCLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1564P
Liquid biopsy in clinical pratice of non-small cell lung cancer (NSCLC): A multi-institutional experience
G. De Maglio1, G. Pasello2, A. Follador3, G. Nardo4, F. Cortiula5, A. Del Conte6, A. D’Urso7, G. Petros8, S. Girlando9, M. Miorin10, V. Polo11, E. Scquizzato12, G. Settanni13, V. Picece14, A. Veccia15, S. Indraccolo16 1 Department of Pathology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, 2Medical Oncology 2, Istituto Oncologico Veneto IRCCS, Padua, Italy, 3Oncology Department, Azienda Sanitaria Universitaria Integrata di Udine - Ospedale Santa Maria della Misericordia, Udine, Italy, 4U.O.C. Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto IRCCS, Padua, Italy, 5Department of Oncology, Azienda Sanitaria Universitaria Integrata di Udine, Udine, Italy, 6S.O.C. Oncologia Medica e dei Tumori Immunocorrelati, Centro di Riferimento Oncologico (CRO) – IRCCS, Aviano, Italy, 7U.O.C. Anatomia Patologica, ULSS1 Dolomiti - Presidio Ospedaliero di Feltre, Feltre, Italy, 8U.O.C. Oncologia, ULSS1 Dolomiti - Presidio Ospedaliero di Feltre, Feltre, Italy, 9Ospedale Santa Chiara, Trento, U.O. Anatomia Patologica, Trento, Italy, 10SSD Genetica medica, AAS5 - Presidio Ospedaliero di Pordenone, Pordenone, Italy, 11Oncology Unit, AULSS 2 Marca Trevigiana, Ca’ Foncello Hospital, Treviso, Italy, 12Dipartimento Interaziendale di Anatomia Patologica, ULSS 2 Marca Trevigiana, Treviso, Italy, 13Servizio di Anatomia-Istologia Patologica, IRCCS Ospedale Sacro Cuore Don Calabria - Negrar, Italy, 14Dipartimento di Oncologia Medica, IRCCS Ospedale Sacro Cuore Don Calabria, Negrar, Italy, 15U.O. Oncologia Medica, Ospedale Santa Chiara, Trento, Italy, 16U.O.C. Immunologia e Diagnostica Molecolare Oncologica, Istituto Oncologico Veneto IOV IRCCS, Padua, Italy Background: Circulating tumor DNA (ctDNA) from liquid biopsy is a source of tumor genetic material for EGFR testing in NSCLC when resistance to I-II generations TKItherapies occurs or upfront, in absence of tissue biopsy. A multi-regional survey for patients treated with EGFR TKI from January to December 2018 was conducted regarding use of liquid biopsy for NSCLC in clinical practice. Methods: Aim of the study was to describe EGFR testing workflow by liquid biopsy in clinical setting. Seven major lung-cancer centers in North Eastern Italy participated to the survey. Results: Overall 316 patients (360 samples) have been screened for ctDNA EGFR, with a medium number of 1.1 samples/patient. All institutions reported EGFR as the main gene tested for clinical purposes in plasma samples of NSCLC, other genes (i.e. KRAS/ BRAF) were occasionally tested upon oncologist request. Seven out of seven (100%) centers used commercially available real time CE-IVD tests. NGS or droplet digital
v644 | NSCLC, Metastatic
PCR were used by one center each, as confirmation methods. In all institutions blood drawing was performed in the same hospital of EGFR testing (in 6/7 - 86%- centers in the Medical Oncology Unit), and plasma separated within 2 hours. EGFR testing was performed in the Surgical Pathology Unit and report edited within 24 hours in 3/7 (43%) centers and within 3-5 working days in 4/7 (57%) centers. Among all, 108 (34%) patients were tested at the time of diagnosis with an EGFR mutation rate of 15%. At progression to TKI treatment, 208 (66%) patients were tested. T790M positive rate was 55/122 (45%). Inconclusive cases (negative for both T790M and known actionable mutation) were 86 (41%). All centers declared that histo/cytological re-biopsy was suggested in these cases. Conclusions: Real-world experiences about EGFR testing in liquid biopsies revealed homogeneous habits among interviewed centers, according to national guidelines and literatures data. The consistent number of liquid biopsies at the time of diagnosis mainly refers to some reference centers that collect specimens from several institutions. However it might impose a revision of bronchoscopy workflows in order to obtain better samples suitable both for cito-histological diagnosis and molecular profiling. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
1565P
A phase III study comparing SB8, a proposed bevacizumab biosimilar, and reference bevacizumab in patients with metastatic or recurrent non-squamous NSCLC
M. Reck1, A. Luft2, I. Bondarenko3, S. Shevnia4, D. Trukhin5, N.V. Kovalenko6, K. Vacharadze7, F. Andrea8, A. Hontsa9, J. Choi10, D. Shin11 1 Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany, 2Department of Thoracic Surgery, Leningrad Regional Clinical Hospital, St. Petersburg, Russian Federation, 3Oncology and Medical Radiology Department, Dnipropetrovsk City Multidisciplinary Clinical Hospital N4, Dnipro, Ukraine, 4Department of Chemotherapy, Podillia Regional Oncology Center, Vinnytsia, Ukraine, 5Oncology Department, Odessa Regional Oncology Center, Odessa, Ukraine, 6Oncology, Volgograd Regional Clinical Oncology Dispensary, Volgograd, Russian Federation, 7Department of Phthisiatry, Research Institute of Clinical Medicine, agos Kor anyi Tbilisi, Georgia, 8Department of Pulmonary Class and Bronchology, Orsz TBC e´s Pulmonol ogiai Inte´zet, Budapest, Hungary, 9Day Staing Department, Chernivtsi 10 Regional Oncology Center, Chernivtsi, Ukraine, Biometrics, Samsung Bioepis Co., Ltd., Suwon, Republic of Korea, 11Medical Affairs, Samsung Bioepis Co., Ltd., Suwon, Republic of Korea Background: SB8 is a proposed biosimilar of the reference bevacizumab (BEV). This study compared the efficacy, safety, pharmacokinetics (PK), and immunogenicity of SB8 to BEV in patients with metastatic or recurrent non-squamous non-small cell lung cancer (NSCLC). Methods: In this randomised, double-blind, multicentre study, patients were randomised (1:1) to receive SB8 or BEV with paclitaxel and carboplatin Q3W followed by SB8 or BEV maintenance therapy until disease progression, unacceptable toxicity, death, or 1 year from the randomisation of the last patient. The primary endpoint was the best overall response rate (ORR) by 24 weeks of chemotherapy; risk ratio was analyzed in the full analysis set (FAS) and risk difference was analyzed in the per-protocol set (PPS). Secondary endpoints were progression free survival (PFS), overall survival (OS), duration of response (DOR), safety, PK, and immunogenicity. Results: A total of 763 patients (SB8, n ¼ 379; BEV, n ¼ 384) were randomized. Baseline characteristics were balanced between SB8 and BEV. In the FAS, the best ORR was 47.6% in SB8 and 42.8% in BEV; the risk ratio was 1.11 and its 90% CI was [0.975, 1.269], which was within the pre-defined equivalence margin of [0.737, 1.357]. In the PPS, the best ORR was 50.1% in SB8 and 44.8% in BEV; the risk difference was 5.3% and its 95% CI was [2.2%, 12.9%], of which the lower margin was contained within and the upper margin was outside the pre-defined equivalence margin of [12.5%, 12.5%]. The secondary efficacy endpoints in the FAS were comparable between SB8 vs BEV: median PFS (8.50 vs 7.90 months), median OS (14.90 vs 15.80 months), and median DOR (5.60 vs 5.85 months). The overall incidence of treatment-emergent adverse events (TEAEs) was comparable between SB8 vs BEV (92.1% vs 91.1%). The most frequently occurring TEAEs were alopecia, anaemia, and nausea. PK parameters (Ctrough and Cmax) and the incidence of overall anti-drug antibodies (16.1% vs 11.0%) were comparable between SB8 vs BEV. Conclusions: This study demonstrated equivalence between SB8 and BEV in terms of best ORR risk ratio. Other efficacy endpoints, safety, PK, and immunogenicity were comparable between SB8 and BEV. Clinical trial identification: NCT02754882. Legal entity responsible for the study: Samsung Bioepis Co., Ltd. Funding: Samsung Bioepis Co., Ltd. Disclosure: M. Reck: Honoraria (self), Advisory / Consultancy: Samsung Bioepis Co., Ltd.; Honoraria (self), Advisory / Consultancy: AbbVie; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Roche. J. Choi: Full / Part-time employment: Samsung Bioepis Co., Ltd. D. Shin: Full /
Volume 30 | Supplement 5 | October 2019
Downloaded from https://academic.oup.com/annonc/article-abstract/30/Supplement_5/mdz260.085/5578305 by guest on 25 October 2019
J. Zhen, L. Wen, S. Li, M. Lai, C. Zhou, L. Cai Department of Oncology, Guangdong Sanjiu 999 Brain Hospital, Guangzhou, China
Annals of Oncology